Dysregulation of intraovarian redox status and steroidogenesis pathway in letrozole-induced PCOS rat model: a possible modulatory role of l-Carnitine

Abstract

Abstract Background Polycystic ovarian syndrome (PCOS) is a reproductive disorder associated with several endocrine and metabolic alterations. The mechanism underlying this syndrome is controversial. On the other hand, drugs used for the treatment are associated with several side effects and poor in controlling PCOS phenotype. l-Carnitine (LC) has been reported to have a significant regulatory function on the redox and metabolic status of female reproductive system. Nevertheless, its regulatory pathways to regulate PCOS are still under investigation. Therefore, this study aimed to evaluate the effects of LC on the steroidogenic pathways, oxidative stress markers and metabolic profile in letrozole (LTZ)-induced PCOS rat model. Methods For this aim, animals were divided into four groups (n = 6). Control group, untreated letrozole-induced PCOS group (1 mg/kg bwt) for 21 days, PCOS group treated with l-Carnitine (100 mg/kg bwt) for 14 days and PCOS group treated with clomiphene citrate (2 mg/kg bwt) for 14 days. Finally, body and ovarian weight, metabolic state(glucose and lipid profile), hormonal assays (testosterone, 17 β estradiol, LH and FSH levels), intraovarian relative gene expression (CYP17A1, StAR, CYP11A1 and CYP19A1 genes), ovarian redox state (malondialdehyde (MDA), reduced glutathione content (GSH) and catalase enzyme activity (CAT)) as well as serum total antioxidant capacity (TAC) were detected. Also, histomorphometric ovarian evaluation (number and diameter of cystic follicles, granulosa cell thickness and theca cell thickness) as well as immune expression of caspase-3 of granulosa cells of cystic follicles were determined. Results LC significantly improved ovarian redox state (GSH, MDA and CAT), steroidogenic pathways gene expression (CYP17A1, StAR, CYP11A1 and CYP19A1 genes), hormonal profile (Follicle stimulating hormone (FSH) and luteinizing hormone (LH), testosterone and estradiol), metabolic state (Glucose and lipid profile) histomorphometric alterations and decreased caspase 3 immune reaction of granulosa cells. Conclusion l-Carnitine supplementation can ameliorate the PCOS phenotype through its energetic, antioxidant and antiapoptotic functions as well as steroidogenesis regulatory role. This protocol could be modified to produce the best therapeutic benefits, and it could be regarded as a prospective therapeutic intervention for PCOS.

Keywords

• Poly-cystic ovary
• l-Carnitine
• Steroidogenesis
• Metabolic state
• Redox state
• Rats